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A Phase I Pharmacokinetic Study Of Epothilone B Analogue BMS-247550 (NSC 710428D) In Patients With Advanced Malignancies And Varying Levels Of Liver Dysfunction

Phase 1
18 Years
Not Enrolling
Lymphoma, Small Intestine Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Pharmacokinetic Study Of Epothilone B Analogue BMS-247550 (NSC 710428D) In Patients With Advanced Malignancies And Varying Levels Of Liver Dysfunction


- Determine the levels of hepatic impairment at which dose modifications of ixabepilone
are required in patients with advanced solid tumors or lymphomas and varying levels of
liver dysfunction.

- Determine the effect of hepatic dysfunction on the plasma pharmacokinetics of this drug
in these patients.

- Determine the toxic effects of this drug at varying levels of hepatic dysfunction in
these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
liver function (normal vs mild dysfunction vs moderate dysfunction vs severe dysfunction).

Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 3 weeks in the
absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of ixabepilone until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at
least 6 but no more than 12 patients are treated at the recommended phase II dose.

Patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 12-84 patients (6-12 for stratum 1; 2-18 for stratum 2; 2-24
for stratum 3; and 2-30 for stratum 4) will be accrued for this study within 12 months.

Inclusion Criteria


- Histologically or cytologically confirmed solid tumor or lymphoma for which standard
curative or palliative measures do not exist or are no longer effective

- Pathological confirmation of diagnosis not required in patients with liver mass,
raised alpha-fetoprotein levels (at least 500 ng/mL), and positive serology for
hepatitis consistent with a diagnosis of hepatocellular carcinoma

- Any solid tumor or lymphoma tumor type eligible

- Must have had thoracic and upper abdominal CT scan, including entire liver and
adrenals, within 28 days before study entry

- Patients with glioma or brain metastases must be on a stable dose of corticosteroids
and be seizure-free for the past month

- Prior whole brain or gamma knife radiotherapy required for known brain

- No unstable or untreated (non-irradiated) brain metastases



- 18 and over

Performance status

- Zubrod 0-2

Life expectancy

- Not specified


- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- No active hemolysis


- See Disease Characteristics

- Patients with biliary obstruction for which a shunt has been placed are allowed if
shunt is in place for at least 10 days and liver function is stable

- Abnormal liver function (bilirubin and SGOT) allowed regardless of cause (metastases
or other causes)

- No evidence of biliary sepsis


- Creatinine no greater than 1.5 mg/dL


- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia


- No concurrent uncontrolled illness

- No ongoing or active infection

- No uncontrolled diarrhea

- No peripheral neuropathy grade II or greater

- No psychiatric illness or social situation that would preclude study compliance

- HIV negative

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception


Biologic therapy

- No concurrent immunotherapy for malignancy


- More than 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

- No other concurrent chemotherapy for malignancy

Endocrine therapy

- See Disease Characteristics

- No concurrent oral contraceptives

- No concurrent hormone therapy for malignancy

- Concurrent luteinizing hormone-releasing hormone agonists allowed


- See Disease Characteristics

- More than 4 weeks since prior radiotherapy and recovered

- No concurrent radiotherapy for malignancy


- More than 2 weeks since prior major surgery


- Recovered from prior therapy

- No concurrent medications that are known to be inhibitors of CYP3A4

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

dose defining

Safety Issue:


Principal Investigator

Angela Davies, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, Davis


United States: Federal Government

Study ID:




Start Date:

October 2003

Completion Date:

December 2007

Related Keywords:

  • Lymphoma
  • Small Intestine Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • anaplastic large cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • intraocular lymphoma
  • primary central nervous system lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent adult Hodgkin lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent adult T-cell leukemia/lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • small intestine lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • stage IV adult Burkitt lymphoma
  • stage IV adult Hodgkin lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV adult T-cell leukemia/lymphoma
  • stage IV cutaneous T-cell non-Hodgkin lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • stage IV marginal zone lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic
  • Liver Diseases
  • Duodenal Neoplasms
  • Ileal Neoplasms
  • Jejunal Neoplasms
  • Intestinal Neoplasms



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